EP1222008A1

EP1222008A1 - Method for supercritical fluid extraction

Info

Publication number: EP1222008A1
Application number: EP00967975A
Authority: EP
Inventors: Philippe Mengal
Original assignee: Hitex
Current assignee: Hitex
Priority date: 1999-10-19
Filing date: 2000-10-06
Publication date: 2002-07-17
Anticipated expiration: 2020-10-06
Also published as: FR2799660B1; WO2001028649A1; AU7795800A; FR2799660A1; CA2387858A1; JP2003516217A; ATE241412T1; EP1222008B1; DE60003057D1

Abstract

The invention relates to a method for extracting one or more active compounds from a starting material using a supercritical fluid, said compounds being for introduction into the formulation of a cosmetic, pharmaceutical or food composition containing at least one excipient. The inventive method comprises the following steps: placing said starting material containing the active compounds in the presence of at least one extraction fluid in a supercritical state and containing CO2 and at least one co-solvent; separating said extraction fluid containing at least a proportion of the active compound(s); causing the CO2 contained in the extraction fluid to vaporize in order to obtain an extract consisting of said co-solvent and said proportion of the active compound(s); recovering the extract consisting of the co-solvent/active compound mixture. The method is characterised in that said co-solvent consists of said excipient.

Description

Extraction process by supercritical fluid.

The invention relates to the field of methods for extracting active compounds from raw materials of natural origin, making it possible to obtain active extracts used in the formulation of cosmetic, pharmaceutical or food compositions.

Natural extracts, obtained in particular from plants, algae, biomass or beehive products, have been used traditionally for a long time in the cosmetic, dermo-pharmaceutical, pharmaceutical or food fields. Many extraction methods are traditionally used to obtain these extracts: hydro-distillation, extraction with organic solvents, hydroglyco maceration, hxiviation, decoction, ...

These traditional processes have advantages, mainly related to the simplicity of the technologies used, but also énients. In this regard, the following problems may be mentioned: presence of residual solvents in the case of extraction with organic solvent; poor stability of the extracts obtained by maceration; very long contact time for rrvdroglycohques macerations, - low selection of the extraction in general, leading to too strong coloring of the extracts. Beyond the “natural product” image, the cosmetic and dermopharmaceutical industry is now looking for very stable products, with selective extracts of active substances. In addition, the cost of extracts must be optimized as much as possible.

We also know that a fluid in a supercritical state, that is to say in a state characterized either by a pressure and a temperature respectively greater than the pressure and the temperature in ticks in the case of a pure body, either by a representative point (pressure, temperature) located beyond the envelope critical points represented on a diagram (pressure, temperature) in the case of a mixture, presents, for very many substances, a high solvent power without common measure with that observed in this same fluid in the state of compressed gas . This is the reason why these fluids are used in many extraction processes (solid / fluid), fractionation (liquid / fluid), analytical or preparative chromatography, treatment of materials (ceramics, polymers, ... ).

In this regard, it should be noted that the physicochemical properties of carbon dioxide (CO ₂ ) as well as its critical coordinates (critical pressure: 7.4 Mpa and critical temperature: 31 ° C) make it the preferred solvent in numerous applications, especially since it does not present any toxicity and is available at a high level of purity in very large quantities and at low prices.

This technology makes it possible to obtain very high quality extracts, tailor-made, according to the choice of operating parameters. In fact, the solvent power of supercritical CO ₂ varies as a function of the pressure and the extraction temperature. Oils rich in polyunsaturated fatty acids or fractions rich in unsaponi iable of very high quality are thus obtained by this technology. The disadvantage of supercritical CO ₂ extraction is the high cost linked to the low solvent power of pure CO ₂ , which limits its application to a few niches. In order to increase the solvent power of supercritical CO ₂ and therefore to increase the productivity of the process, a co-solvent such as ethanol, methanol or acetone can be added to the supercritical CO ₂ . The solvent power of supercritical CO ₂ can then be increased by a factor of 10. Unfortunately, the productivity gain is offset by the need to remove the solvent from the extract, which on the one hand involves an additional distillation operation. / drying, and on the other hand often causes stability problems. The main objective of the present invention is to propose a new method of extraction with supercntic CO ₂ which does not have the above-mentioned drawback.

The objective of the present invention is also to propose such a simpler method than the methods of extraction by supercritical fluid of the prior art.

These objectives are achieved thanks to the invention which relates to a process for the extraction by supercritical fluid of one or more active compounds intended to enter into the formulation of a cosmetic, pharmaceutical or food composition containing at least one excipient, from a raw material, said method comprising the steps of; bringing said raw material containing the active compounds into contact in the presence of at least one extraction fluid in the supercritical state comprising CO ₂ and at least one co-solvent, - separating said extraction fluid containing at least part active compound (s); causing the CO ₂ contained in the extraction fluid to vaporize in order to obtain an extract consisting of said co-solvent and of said part of the active compound (s); - recovering said extract constituted by the co-solvent / compound (s) actιf (s) mixture; characterized in that, said co-solvent consists of said excipient.

The present invention is therefore based on the discovery that certain excipients compatible with cosmetic, dermo-pharmaceutical, pharmaceutical or food use can be used in admixture with supercritical CO ₂ . This mixture then behaves like a fluid whose solvent power can be adjusted by modifying the proportion CO ₂ / excιpιent or by adapting the pressure and the extraction temperature. The invention therefore uses the properties of supercπtic fluids or pressurized liquids, to which an excipient has been added, and having, under appropriate temperature and pressure conditions, an increased dissolving power with respect to the active agents to be extracted. , better selectivity while considerably limiting the risks of degradation of the active compounds, these being protected during the extraction process

The excipient-active mixture can moreover correspond to the final formulation, which constitutes an important advantage.

According to a preferred aspect of the invention, the method according to the latter comprises an additional step consisting in recycling the vaporized CO ₂ , at the head of the process where it can be condensed, pumped and reheated so as to be passed back to the supercntic state .

According to a vanante, the method comprises a preliminary step consisting in adding said excipient to CO ₂ in the supercritical state to obtain said extraction fluid.

According to another variant, the method comprises a preliminary step consisting in adding said excipient to the liquid CO ₂ under pressure and then heating the mixture obtained in order to pass the CO ₂ to the supercritical state and to obtain said extraction fluid. According to another preferred aspect of the invention, said extraction fluid has a compressed temperature between approximately 31 ° C. and approximately 100 ° C. and a compressed pressure between approximately 7.4 MPa and approximately 50 MPa.

The excipients which can be used within the framework of the present invention can be any compound or mixture of compounds compatible with cosmetic, dermo-pharmaceutical, pharmaceutical or food use having sufficient solubility in CO ₂ under pressure. Thus glycerol, an excipient conventionally used in cosmetics, which is considerably insoluble in CO ₂ , cannot be chosen while other compounds having a low but not zero solubility can be validly used. Preferably, depending on whether the formulation is intended for a cosmetic, pharmaceutical, dermo-pharmaceutical or food product, said excipient is chosen from the group consisting of, propylene glycol, butylene glycol, polyethylene glycols of all molecular weights, monoethyl ether diethylene glycol, hexvlene glycol, polyols, glycemic fatty substances, non-glycemic fatty substances, esters, waxes, silicone oils and terpec compounds.

Advantageously, the method according to the invention is implemented with weight proportions (raw material) / (CO ₂ ) / (Excιpιent) of (10) / (10 to 2000) / (l to 200).

The invention also relates to any extract obtained by a single extraction process characterized in that it consists of one or more active compounds and by at least one excipient used in the formulation of a cosmetic, pharmaceutical or food product. The extracts obtained by the process which is the subject of the present invention can be used in any galemic form used in cosmetics or dermopharmaceuticals: oil in water and water in oil emulsion, shampoos and conditioners, milks, lotions, gels, ointments, hair sprays , without this list being exhaustive. They can also be used in the food and pharmaceutical fields.

It is possible to incorporate the extracts obtained by the process which is the subject of the present invention into cosmetic vectors such as liposomes, chylomicrons, macro, micro and nanoparticles, as well as macro, micro, nanocapsules. They can be absorbed on powdery organic polymers, talcs, bentonites and other mineral supports.

The extracts obtained by the process which is the subject of the present invention can be combined in cosmetic compositions with any other ingredient usually used in cosmetics and dermopharmaceuticals: lipids, polymers gelling agents and viscosants, surfactants and emulsifiers, hydro or liposoluble active ingredients, extracts from other raw materials.

The cosmetic or dermopharmaceutical compositions containing the extracts obtained by the process which is the subject of the present invention are intended for all cometic and dermopharmaceutical applications, namely in particular: care and hygiene of the skin, scalp, hair, mucous membranes, oral regions, for anti-aging treatments and sun protection, for hydration, smoothing effect or any other application.

The invention, as well as the advantages which it presents, will be more easily understood thanks to the exemplary embodiments thereof set out below.

EXAMPLE 1

The present example constitutes a comparative example between the traditional extraction with supercritical CO ₂ and the extraction, according to a variant of the process which is the subject of the present invention, of ginger extract.

According to the conventional process, the extraction with supercritical CO ₂ is carried out without co-solvent at 300 bar and 50 ° C. 9 g of extract are collected by percolating 6 kg of CO ₂ on 30 g of ginger previously ground and 11 g of extract are collected by percolating 12 kg of CO ₂ . Under these conditions, the extract obtained pasty and "sticky" has a strong odor and flavor, characteristic of the raw material, while the residue is almost deodorized.

According to the invention, the process is then carried out under the same pressure and temperature conditions but in the presence of a co-solvent, namely propylene glycol, in mixture with CO ₂ at a rate of 10 g per 1 kg of CO ₂ .

The use of a co-solvent makes it possible to increase the performance of the extraction process.

More specifically, thanks to the invention, 5 kg of CO ₂ propylene glycol mixture are sufficient to obtain a product consisting of ginger extract and propylene glycol having an aromatic power (for example according to the index Scov ille as defined in the book "Spices and herbs" (Lavoisier editions - 1992) equivalent to that of the extract obtained without co-solvent using 12 kg of CO ₂ . In addition, the product obtained thanks to the invention, contains as an excipient the co-solvent and therefore has a fluid appearance, which makes it much easier to handle and formulate in a food preparation.

EXAMPLE 2

In this example, the traditional extraction with supercritical CO ₂ of white pepper is compared with the extraction according to a method of the process which is the subject of the present invention.

In extraction with supercntic CO ₂ without co-solvent at 300 bar and 40 ° C, 10 g of extract are collected by percolating 20 kg of CO ₂ on 500 g of crushed white pepper. Under these conditions, the extract obtained with a resinous appearance has a powerful and pungent flavor, characteristic of the raw material. Under the same pressure and temperature conditions, the addition of propylene glycol at the rate of 10 g per 1 kg of CO ₂ makes it possible to increase the performance of the process. Under these conditions, 10 kg of CO ₂ propylene glycol mixture are sufficient to obtain the same flavoring power, while the extract obtained, of fluid appearance, is easy to handle and to formulate in a food preparation.

EXAMPLE 3

This example is a summary of Example 2 for which the propylene glycol is replaced by peanut oil added to 5 g per kg of CO ₂ . The extract obtained, with an oily appearance, is particularly suitable for the formulation of food preparation in the presence of other fatty substances. EXAMPLE 4

In this example, the traditional extraction with supercritical CO ₂ of paprika powder is compared with the extraction according to a variant of the process which is the subject of the present invention. In extraction with supercritical CO ₂ without co-solvent at 300 bar and 60 ° C, the extract yield is very low, even for large quantities and percolated CO ₂ .

By adding to the CO ₂ , 5% of ethyl alcohol to increase the solvent power, 30 kg of CO ₂ + alcohol mixture are necessary to obtain a "color yield" of 50 g of oleoresism at 110,000 UC (UC: Units Color according to the American Spice Trade Association Analytical Methods (1986) / ASTAA New-York Method No. 20.0) standard, for 1 kg of papnka after evaporating the alcohol.

By implementing the process which is the subject of the present invention by adding 5 g of propylene glycol per kg of CO ₂ , the same color yield is achieved for 25 kg of CO ₂ propylene glycol mixture for 1 kg of paprika. The extract collected by decantation, including the co-solvent, has a color yield of more than 200,000 UC, without the need to evaporate the co-solvent.

EXAMPLE 5

In this example, the traditional supercritical CO ₂ extraction of parthenoid from Tanacetum parthenium is compared to the extraction according to a method of the process which is the subject of the present invention. In extraction with supercntic CO ₂ without co-solvent at 300 bar and 40 ° C, 14.8 g of dark green extract and resinous appearance are collected by percolating 8 kg of CO ₂ on 300 g of ground drug. The extract analyzed by Gas Chromatography has a 14.5% parthenoid content. The parthenoid yield is therefore 14.8 x 0.145 / 300 = 0.715%. The batch of plant used titrating 0.8% in parthenohde, we can consider that 90% was extracted. In order to increase its conservation and allow the formulation of this extract in soft capsule, the raw extract must be diluted with a glyceride oil.

Under the same pressure and temperature conditions, the extraction was carried out by adding to the CO ₂ 0.5% of a mixture of triglycerides of capric and caprylic acids. By percolating 6 kg of this mixture successively on 300 g of drug and then 1 kg of pure CO ₂ , 40.5 g of weakly colored oily extract are collected. This extract titrating 5.5% (m / m) of parthenolide, it can be formulated as it is and packaged in soft capsule.

EXAMPLE 6

In this example, the traditional extraction with supercritical CO ₂ of kawa lactones of kawa-kawa (Piper methysticum) is compared with the extraction according to a variant of the process which is the subject of the present invention.

In extraction with supercritical CO ₂ without co-solvent at 300 bar and 40 ° C, 21.5 g of viscous orange-yellow extract are collected by percolating 10 kg of CO2 on 350 g of ground plant. The extract analyzed by HPLC titers 85% in total kawa lactones. This extract must then be standardized to 30% kawa lactones by mixing it with an excipient.

By carrying out the extraction according to the process which is the subject of the present invention by adding 2% (m / m) of capric and caprylic acid triglycerides to the CO2, the bright yellow collected extract of oily appearance is standardized to 30% kawa. lactones by limiting the loss of active ingredient by degradation.

EXAMPLE 7 In this example, the traditional extraction with supercritical CO ₂ of Calendula flowers is compared with the extraction according to a variant of the process which is the subject of the present invention.

By supercritical CO2 extraction to which 3% of a mixture of capric and caprylic acid triglycerides are added, kinetics are observed. of lutein extraction used as a tracer twice as fast as by extraction with CO ₂ without excipient. In addition, the extract obtained by the process which is the subject of the present invention is much easier to use in dermopharmaceutical and cosmetic preparations.

EXAMPLE 8

This example is a variant of Example 7 for which part of the water contained in the Calendula flowers is co-extracted. The extract then offers the appearance of an emulsion whose properties are of interest in dermo-pharmaceutical and cosmetic preparations.

The embodiments of the invention described here are in no way intended to reduce the scope of the invention. Many modifications can therefore be made to it without going beyond the scope of these.

Claims

1. Process for the extraction by supercritical fluid of one or more active compounds intended to enter into the formulation of a cosmetic, pharmaceutical or food composition containing at least one excipient, from a raw material, said process comprising the steps of; contacting said raw material containing the active compounds in the presence of at least one extraction fluid in the supercritical state comprising CO ₂ and at least one co-solvent, separating said extraction fluid containing at least part of the or active compounds; causing the CO ₂ contained in the extraction fluid to vaporize in order to obtain an extract consisting of said co-solvent and of said part of the active compound (s); recovering said extract consisting of the co-solvent / active compound (s) mixture; characterized in that, said co-solvent consists of said excipient.

2. Method according to claim 1 characterized in that it comprises a step consisting in recycling the vaporized CO ₂ .

3. Method according to any one of claims 1 or 2 characterized in that it comprises a preliminary step consisting in adding said excipient to CO ₂ in the supercritical state to obtain said extraction fluid.

4. Method according to any one of claims 1 or 2 characterized in that it comprises a preliminary step consisting of adding said excipient to the liquid CO ₂ under pressure and then heating the mixture obtained to bring the CO ₂ to the state supercritical and obtain said extraction fluid.

5. Method according to any one of claims 1 to 4 characterized in that said extraction fluid has a temperature between about 31 ° C and about 100 ° C and a pressure between about 7.4 MPa and about 50 MPa .

6. Method according to any one of claims 1 to 5 characterized in that said excipient is chosen from the group consisting of said excipient is chosen from the group consisting of, propylene glycol, butylene glycol, polyethylene glycols of all weights molecular, monoethyl ether of diethylene glycol, hexylene glycol, polyols, fatty fatty acids, non-fatty fatty substances, esters, waxes, silicone oils and terpene compounds.

7. Method according to any one of claims 1 to 6 characterized in that it is implemented with weight proportions (raw material) / (CO ₂ ) / (excipient) of (10) / (10 to 2000) / (l to 200).

8. Extract obtained by the extraction process according to any one of claims 1 to 7, characterized in that it consists of one or more active compounds and by at least one excipient used in the formulation of a cosmetic compound, pharmaceutical or food.